Abstract (english)

The cellular prion protein, PrPC, is a membrane-bound glycoprotein abundantly expressed in neurons, and highly conserved among mammals. Its bad reputation originates from the discovery that, following a misfolding process, PrPC is converted into the pathogenic PrPSc isoform. PrPSc has novel physico-chemical and biologic properties, and is the main component of prions, the etiological agents of transmissible spongiform encephalopathies (TSE), which are fatal to both men and animals.
Although much is known about the involvement of PrPSc in the onset of TSE, the mechanisms of PrPSc-mediated neurodegeneration and the physiologic function of PrPC are still obscure. Several lines of evidence have attributed to PrPC a plethora of different biologic potentials, possibly by taking part in the activation of signalling pathways. The most reasonable hypothesis for this multi-faceted behaviour is that its function includes an additional multi-potent factor capable of controlling several cell events. Our working hypothesis is that this factor is Ca2+, the pleiotropic carrier of signals that controls the balance between the life and death of the cell.
In this work, we have probed the hypothesis by comparing, in primary cultures of cerebellar granule cells derived from wild-type and PrP-knockout mice, local Ca2+ movements, and the expression of major Ca2+-transporting systems. Measurements of Ca2+ fluxes have been accomplished by using recombinant aequorin, a Ca2+-sensitive photo-protein, genetically targeted to different cellular domains, i.e., the plasma membrane, the lumen of the endoplasmic reticulum and the matrix of mitochondria.
We found that, with respect to the presence of the protein, the absence of PrPC causes alterations of local Ca2+ movements, and of the expression of channels and pumps selective for the ion. These results may thus allow to conclude that, given the clear intervention of PrPC in Ca2+ homeostasis, PrPC may be part of the cellular system(s) deputed to avoid the toxic accumulation of Ca2+ in the cell.

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